Studies will continue on the mechanism of action of the release of catecholamines, by carboxylic ionophores such as monensin, from isolated, cultured bovine chromaffin cells. We intend measuring alterations of intracellular ion contents and fluxes, in response to monensin, in order to test the hypothesis that the ionophore acts by increasing intracellular sodium activity in some compartment which responds by releasing intracellular calcium thereby stimulating cellular secretion. The ionic responses will be compared with those evoked by more conventional secretogogues, e.g., carbachol. The technique will involve measuring the uptake of radioactive 22Na ion or 45Ca2 ion or the release of these ions from pre-equilibrating cells. Catecholamines are measured as the release of labeled catecholamine from pre-equilibrated cells. These ionic determinations will also be paralleled by studies of the isolated perfused heart utilizing a strength of contraction as a biological correlate. We also intend commencing a search for homologies between the proteins of chromaffin granule membranes and other secretory granules, e.g., zymogen granules, liver secretory granules etc.